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A NOVEL REGULATOR OF CANCER CELL MIGRATION AND INVASION

Award Number: R01CA115706
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/25/2006
PERIOD OF PERFORMANCE END DATE: 05/31/2014

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A NOVEL REGULATOR OF CANCER CELL MIGRATION AND INVASION - DESCRIPTION (provided by applicant): Regulation of the cytoskeleton and cell migration is an important aspect of cancer invasion and metastasis. This project focuses on a novel protein, Nischarin that has an inhibitory role in cell migration and invasion. Integrins have been implicated in cellular processes including the organization of actin cytoskeleton, cell growth and survival, cell motility and cell invasion. We have identified a novel protein that specifically interacts with the a5 cytoplasmic tail; we have termed this protein 'Nischarin'. Recently, with the help of effector domain mutants of Rac1, we demonstrated that Nischarin selectively inhibits Rac-driven signaling cascades that act through p21 activated kinase (PAK). These observations suggest that Nischarin affects the process of cytoskeletal regulation mediated by Rac and PAK. Consistent with this, Nischarin binds to PAK, and inhibits the kinase activity of PAK. Furthermore, our recent data indicate that Nischarin siRNA stimulates lamellipodia formation and cell migration, and activates PAK kinase, suggesting that Nischarin is an important regulator of cell motility. The intent of the proposal is to investigate further the newly described biochemical connection between PAK and Nischarin and its role in tumor cell migration and invasion. In Aim I we will address the role of Nischarin in the migration and invasion of carcinoma cells by over or underexpressing Nischarin. Also we will examine spatio-temporal localization and regulation of PAK and Nischarin in pseudopodia and invadopodia. In Aim II, we will study the effect of Nischarin on downstream effectors of PAK including LIMK and cofilin, and will examine how this affects invasion of cancer cells. In Aim we will evaluate Nischarin's effects on lamellipodia formation by studying lamellipodial dynamics with live cell imaging; we will visualize the effects on lamellipodial protrusion, lamellipodial retraction and membrane ruffles. Evaluation of the role of Nischarin and PAK in the regulation of tumor cell migration and invasion will broaden the current understanding of PAK signaling in carcinoma cells, and may provide new avenues for therapeutic intervention.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2010	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	5	4/23/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2010	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	5	4/18/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2010 ( Subtotal = $195,792 )
2010	2010	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	5	4/30/2010	NON-COMPETING CONTINUATION	$195,792
														Subtotal = $195,792

Issue Date FY: 2009 ( Subtotal = $195,792 )
2009	2009	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	4	6/5/2009	NON-COMPETING CONTINUATION	$195,792
														Subtotal = $195,792

Issue Date FY: 2008 ( Subtotal = $215,746 )
2008	2008	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	3	5/19/2008	NON-COMPETING CONTINUATION	$215,746
														Subtotal = $215,746

Issue Date FY: 2007 ( Subtotal = $195,792 )
2007	2007	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	2	5/8/2007	NON-COMPETING CONTINUATION	$195,792
														Subtotal = $195,792

Issue Date FY: 2006 ( Subtotal = $201,640 )
2006	2006	LSU HEALTH SCIENCES CENTER/NIH	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cancer Biology Research	000	1	7/25/2006	NEW	$201,640
														Subtotal = $201,640

Grand Total All Awards = $1,004,762

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A NOVEL REGULATOR OF CANCER CELL MIGRATION AND INVASION

Award Number: R01CA115706

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/25/2006

PERIOD OF PERFORMANCE END DATE: 05/31/2014

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